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Mutational uncoupling of alpha1A-adrenergic receptors from G proteins also uncouples mitogenic and transcriptional responses in PC12 cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lee, Deborah L. Robeva, Anna S. Chen, Zhongjian Minneman, Kenneth P. |
| Copyright Year | 2003 |
| Abstract | Activation of human alpha1A-adrenergic receptors in PC12 cells causes many second messenger, mitogenic, and transcriptional responses. We examined the role of G protein activation in these responses by uncoupling the receptor through deletion of the first three amino acids from the third intracellular loop (Delta208-210). Expression levels of retrovirus-transfected wild-type and Delta(208-210) alpha1A-adrenergic receptors in PC12 cells were similar and showed identical binding affinities for antagonists. However, the potency of the agonist norepinephrine was increased 9-fold by the Delta (208-210) mutation. In PC12 cells expressing the Delta (208-210) construct, calcium and inositol phosphate responses to norepinephrine were essentially abolished. The strong activation of mitogen-activated protein kinase pathways seen upon stimulation of wild-type alpha1A-adrenergic receptors in PC12 cells was abolished by the Delta (208-210) mutation, as was activation of the tyrosine kinase Pyk2. Norepinephrine also activates several transcriptional reporters through alpha1A-adrenergic receptors in PC12 cells, including reporters for activator protein 1, serum response element, cAMP response element, nuclear factor-kappaB, nuclear factor of activated T cells, gamma-interferon-activated sequence, and signal transducer and activator of transcription. All these transcriptional responses were abolished by the Delta (208-210) mutation. Overexpression of Galpha16 did not rescue any of these responses. These data suggest that known second messenger, mitogenic, and transcriptional effects of alpha1A-adrenergic receptors in PC12 cells all require G protein activation. |
| Starting Page | 629 |
| Ending Page | 648 |
| Page Count | 20 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jpet.aspetjournals.org/content/jpet/early/2003/04/30/jpet.103.050500.full.pdf |
| PubMed reference number | 12724349v1 |
| Volume Number | 306 |
| Issue Number | 2 |
| Journal | The Journal of pharmacology and experimental therapeutics |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Receptor Amino Acids CELF Proteins Calcium Deletion Mutation Inositol Phosphates Interferon Type II Mitogen-Activated Protein Kinases Mitogens Norepinephrine Protein Tyrosine Kinase Response Elements Transcription, Genetic Transducers second messenger |
| Content Type | Text |
| Resource Type | Article |
